Dataset Information

Identification of homophilic ATP1A1 interaction between tumor cells and fibroblasts

ABSTRACT: Tumor cells with diverse phenotype and biological behaviors are influenced by stromal cells through secretory factors or direct cell-cell contact. Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia with fibroblasts as the major cell type. Here, we observed enrichment of myofibroblasts in juxta-tumoral position, where tumor cells gain epithelial-mesenchymal transition for invasion, that correlated with worsened prognosis in PDAC patients. Direct cell-cell contacts as forming heterocellular aggregates between fibroblasts and tumor cells were detected in primary pancreatic tumors and circulating tumor microemboli. Mechanistically, the overexpressed ATP1A1 of tumor cells binds to and reorganizes ATP1A1 of fibroblasts inducing calcium oscillations, NF-κB activation, and activin A secretion. Consequentially, either silencing ATP1A1 expression or neutralizing activin A secretion suppresses tumor invasion and colonization. Taken together, these results elucidate the mechanic interplay between tumor cells and the bound fibroblasts in PDAC progression, and provide opportunities for potential therapeutic strategy against tumor metastasis by blocking such interaction.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Epithelium Of Pancreatic Duct, Pancreatic Stellate Cell

DISEASE(S): Pancreatic Ductal Adenocarcinoma

SUBMITTER: Yi-Ing Chen

LAB HEAD: Wen-Hwa Lee

PROVIDER: PXD029467 | Pride | 2022-06-09

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	EXP1_tumor_ATP1A1_1_no_crosslink_control.raw	Raw
	EXP1_tumor_ATP1A1_2_BxPC3.raw	Raw
	EXP1_tumor_ATP1A1_3_SU8686.raw	Raw
	EXP1_tumor_ATP1A1_4_MIAPaCa2.raw	Raw
	EXP1_tumor_ATP1A1_5_PANC1.raw	Raw

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Publications

Homophilic ATP1A1 binding induces activin A secretion to promote EMT of tumor cells and myofibroblast activation.

Chen Yi-Ing YI Chang Chin-Chun CC Hsu Min-Fen MF Jeng Yung-Ming YM Tien Yu-Wen YW Chang Ming-Chu MC Chang Yu-Ting YT Hu Chun-Mei CM Lee Wen-Hwa WH

Nature communications 20220526 1

Tumor cells with diverse phenotypes and biological behaviors are influenced by stromal cells through secretory factors or direct cell-cell contact. Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia with fibroblasts as the major cell type. In the present study, we observe enrichment of myofibroblasts in a juxta-tumoral position with tumor cells undergoing epithelial-mesenchymal transition (EMT) that facilitates invasion and correlates with a worse clinical prognosi ...[more]

PMID: 35618735

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